Medical Journal of Dr. D.Y. Patil Vidyapeeth

: 2017  |  Volume : 10  |  Issue : 6  |  Page : 582--584

Crystals hold the clue

Asha K Varghese, TS Shibu, M Pushpalatha 
 Department of Biochemistry, Government Medical College, Thrissur, Kerala, India

Correspondence Address:
Dr. Asha K Varghese
Department of Biochemistry, Government Medical College, Thrissur - 680 581, Kerala


A 21-day-old male infant, born as the first child to a nonconsanguineous couple, presented with nonspecific symptoms, signs, and superimposed infection. Investigations conducted were not conclusive to arrive at a diagnosis. In 6 days, the infant succumbed to his condition. Postmortem samples were analyzed for metabolic substances, and liver biopsy was done. Urine metabolic screening showed the presence of amino acids and reducing substance. Further analysis proved the presence of galactose, generalized aminoaciduria, and liver biopsy with features of inborn error of metabolism. Further samples for higher investigations were not available, which draws attention to the need of being able to diagnose the condition early enough to save lives. We are suggesting a helpful, easy to perform, and cheap diagnostic test algorithm for diagnosing galactosemia in resource-poor settings.

How to cite this article:
Varghese AK, Shibu T S, Pushpalatha M. Crystals hold the clue.Med J DY Patil Univ 2017;10:582-584

How to cite this URL:
Varghese AK, Shibu T S, Pushpalatha M. Crystals hold the clue. Med J DY Patil Univ [serial online] 2017 [cited 2022 Sep 25 ];10:582-584
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Full Text


Inborn errors of metabolism are disorders which have features similar to each other and to that of infection, infestation, and intoxication. Good clinical acumen and competent laboratory are mandatory for early diagnosis and prompt intervention. The deranged metabolic pathway of common biological compounds cause deficiency of substances, accumulation of metabolic intermediates and undesired products formed from alternate metabolic pathways. These hinder and interrupt normal functioning of the human body.[1],[2]

We came across an interesting and rare condition which was diagnosed at our laboratory. We would like to highlight a seldom used testing algorithm for diagnosing the same even in a resource-poor setting.

 Case Report

A 21-day-old male infant was referred to our tertiary care center with the complaints of refractory hypoglycemia, jaundice, loose stools, and superimposed Candida albicans infection. The patient on presentation had tachypnea with normal oxygen saturation, hypotonia, and other systemic examination was normal. The child was born as the first child to a nonconsanguineous couple, after a previous first trimester abortion, with uneventful pregnancy, spontaneous onset of labor, and normal vaginal delivery at a primary health center. On day 1, the child developed fever and jaundice, and after ruling out maternal causes, the patient was referred to a higher center. At the higher center, the patient's jaundice subsided with phototherapy, but he developed seizures, loose stools, and later C. albicans infection. When they found refractory hypoglycemia and rapidly worsening condition, the patient was referred to a tertiary care center. The patient had normal liver function test, electrolytes, negative urine sugar, and ketone bodies. Regular expressed breast milk was given along with supplements. His condition worsened, requiring intensive care unit admission. Anemia was noticed and two subsequent matched blood transfusions were given. Electrolyte imbalance was corrected. The patient succumbed to the sepsis in spite of supportive management. No diagnosis could be reached at the time of demise. Postmortem urine sample was sent directly by bladder syringing, for metabolic screening. Liver tissue was sent for biopsy. Urine metabolic preliminary screening tests showed the presence of amino acids by ninhydrin test and reducing substances by Benedict's test. Common amino acidurias were ruled out. Urine amino acid chromatography result was generalized aminoaciduria when compared to an age-matched control. The most common reducing substance seen in urine was glucose, and for that, specific enzymatic test – glucose oxidase-peroxidase test was done, which reported negative. Sugar chromatography was done with the common reducing sugar standards. A spot corresponding to galactose standard was obtained. Osazone test yielded characteristic rhombic-shaped crystals arranged in the form of cartwheel which was similar to that with galactose standard [Figure 1] and [Figure 2]. There was no sample available for further confirmatory tests – mucic acid test and red blood cell enzyme assay. Liver biopsy result was nonconclusive but showed features of inborn error of metabolism. This brought us to conclude that the infant had an inborn error of metabolizing the reducing sugar galactose, which was inadvertently introduced into the body in the form of breast milk. From the rapid progression of the condition, it might have been complete deficiency of galactose-1-phosphate transferase termed “classic galactosemia.”{Figure 1}{Figure 2}


Galactosemia is an autosomal recessive metabolic disorder of carbohydrates, involving defective galactose-degrading enzymes – galactokinase, galactose-1-uridyl transferase, or Uridine diphosphate (UDP)-galactose epimerase. The sources of galactose in human beings are both endogenous (from breakdown of tissue glycoproteins and glycolipids) and exogenous (mostly from milk protein lactose which is broken down by intestinal flora into monomers, glucose and galactose). The pathophysiology lies in the body's lack of enzymes in Leloir pathway, to convert galactose into glucose and thus getting utilized. The accumulated galactose and its metabolites from alternative pathways cause tissue damage, especially in the liver, brain, and kidneys. Liver dysfunction causes refractory hypoglycemia and progresses soon to severe liver dysfunction and cirrhosis.[3],[4] One of the metabolites, galactitol, gets irreversibly deposited in ocular lens, causing zonular cataracts. Accumulation in white blood cell decreases its bactericidal activity and predisposes to Gram-negative sepsis. It has been found that the damage starts in utero and gets worsened by milk intake after birth. By restricting lactose during pregnancy and following birth, the damages caused by the sepsis, clinically significant cataract, and severe liver dysfunction can be prevented.[5] The neurological and ovarian dysfunctions seem to be unaffected by diet control. In certain less symptomatic disease variants, like the Duarte type, the patient survives to adulthood.[6]

In this case, the presentation of the male infant with neonatal jaundice was treated successfully as physiological jaundice. Subsequent refractory hypoglycemia and high serum insulin level and C. albicans sepsis with pneumonia made it difficult to understand the basic pathophysiology within the short span of time within which the patient succumbed. A report of absent urine-reducing sugars led the treating clinician to rule out carbohydrate-metabolizing defect. The fulminant C. albicans sepsis and pneumonia further made it difficult to delineate the symptoms of the underlying condition.

Looking back, refractory hypoglycemia presenting in the 1st week of life with worsening clinical condition and no obvious noxious factors point toward two differential diagnosis –glycogen storage disorders and galactosemia.[7] A history of one previous spontaneous abortion was a pointer toward a possible genetic defect. The nonspecific symptoms of vomiting, diarrhea, lethargy, failure to thrive, and seizures requiring multiple antiseizure medications indicated an ongoing pathology which was fueled by the milk intake. Both the conditions can present with similar clinical picture and clinicians depend on laboratory evidence to arrive at a definitive diagnosis. Enzyme assays are the answer to both, but it is not available at our setup. Microscopic examination of the liver tissue after differential staining can help to rule out one condition, but it is an invasive procedure and in this case was inconclusive. It however showed features of a metabolic disorder. Paper chromatography which finally helped to arrive at a diagnosis is only a surrogate test and had to be relied on, by which time the patient had expired. Galactosazone crystals seen in the urine sample were conclusive as the uniquely shaped crystals are diagnostic on their own. No further sample could be obtained for further confirmatory tests for galactose.

It called for the laboratory to try out the old and seldom used techniques in the absence of modern facilities to aid the clinician. We are putting forth a simple, economical diagnostic test algorithm for galactosemia, which can be performed by any medical practitioner as a bedside test [Figure 3].{Figure 3}

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

The laboratory supplies provided by Government of Kerala were used for the tests done as part of routine laboratory investigations.

Conflicts of interest

There are no conflicts of interest.


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