Year : 2016 | Volume
: 9 | Issue : 3 | Page : 391--392
Lysinuric protein intolerance in a 5-month-old girl
Viplav Narayan Deogaonkar, Ira Shah
Pediatric Liver Clinic, B J Wadia Hospital for Children, Mumbai, Maharashtra, India
1/B Saguna, 271/B St Francis Road, Vile Parle (W), Mumbai, 400056
Lysinuric protein intolerance (LPI), also known as cationic aminoaciduria, hyperdibasic aminoaciduria type 2, or familial protein intolerance, is an autosomal recessive defect of diamino acid transport. LPI is characterized by the inability of the body to digest and utilize certain amino acids, namely lysine, arginine, and ornithine. As a result, there is an increased excretion of these amino acids, which in turn affects the liver, the gastrointestinal tract, lungs, immune system, spleen, and organs producing blood. We report a 5-month-old girl born of third degree consanguineous marriage who presented with hepatosplenomegaly with sepsis and worsening jaundice due to LPI.
|How to cite this article:|
Deogaonkar VN, Shah I. Lysinuric protein intolerance in a 5-month-old girl.Med J DY Patil Univ 2016;9:391-392
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Deogaonkar VN, Shah I. Lysinuric protein intolerance in a 5-month-old girl. Med J DY Patil Univ [serial online] 2016 [cited 2023 Feb 1 ];9:391-392
Available from: https://www.mjdrdypu.org/text.asp?2016/9/3/391/182517
Lysinuric protein intolerance (LPI) is a congenital metabolic disease affecting many organs. The metabolic disturbance caused in LPI causes increased renal excretion and reduced absorption from the intestine of cationic amino acids, such as lysine, arginine, and ornithine.  LPI is caused by mutations of solute carrier family 7A member 7(SLC7A7) located at chromosome 14q11.2,  which causes defective cationic amino acid transport at the basolateral membrane of epithelial cells in the kidney and intestine. The presence of the transport defect in the hepatocytes distinguishes LPI from other hyperdibasicaminoacidurias.  Here, we present a 5-month-old girl born of third degree consanguineous marriage who had progressive neonatal cholestasis. She was diagnosed to have LPI on the basis of elevated lysine and arginine in urine.
A 5-month-old girl born of third degree consanguineous marriage presented with skin pustules for 15 days and decreased feeding for 2 days. Birth history was normal, and birth weight was 2 kg. On examination, weight was 2.5 kg, length was 46 cm, and she had hepatosplenomegaly. Other systems were normal. Investigations revealed hemoglobin of 6.6 g/dl, white blood cell count of 21,200 cells/cumm (58% polymorphs and 41% lymphocytes), platelets of 180,000 cells/cumm, bilirubin 3.2 mg/dl (direct = 1.7 mg/dl), serum glutamic oxaloacetic transaminase (SGOT) of 80 IU/L, serum glutamic pyruvate transaminase (SGPT) of 34 IU/L, total proteins of 4 g/dl, albumin of 2 g/dl, prothrombin time of 19.3 sec and partial thromboplastin time of 48.3 s, gamma-glutamyl transferase (GGTP) of 82 IU/L, and alkaline phosphatase of 521 IU/L. Blood culture grew Escherichia coli. She was treated with intravenous (IV) fluids, IV antibiotics, fresh frozen plasma, and packed cell transfusion. On starting feeds on day 10 of hospitalization, her bilirubin increased to 24.2 mg/dl (direct = 11.5 mg/dl), SGOT to 160 IU/L, SGPT to 66 IU/L, and serum ammonia increased to 160. Suspecting an underlying metabolic disorder, a metabolic screening was done that showed increased lactate dehydrogenase (1240 UIL), triglycerides (289 mg%), ferritin (3642 ng/dl), normal urine metabolic reducing substance test, normal galactose levels in blood (9.79 mg%), normal serum biotinidase enzyme (5.47 nmol/min), normal urine orotic acid (2.2 µmol/mmol creatinine), normal plasma aminoacidogram and elevated lysine (345 µmol/mmol creatinine), and arginine (134) in urine suggestive of LPI. The patient was treated with protein restriction, sodium benzoate and carnitine supplements, and advised regular follow-up.
LPI is a rare disorder, and only over 140 individuals with LPI have been reported in the world, of which one-third are of Finnish origin.  An LPI patient usually comes with hepatosplenomegaly, failure to thrive, aversion to protein rich food, and poor feeding. Long-term protein restriction and citrulline and nitrogen scavenging drugs are the drugs of choice. The prevention and treatment of the complications such as lung, renal, and musculoskeletal system are also an important part of managing LPI. Being an autosomal recessive disorder, genetic counseling can form an important part of the management.
Our patient presented after weaning with symptoms such as vomiting, diarrhea, poor feeding, failure to thrive, enlargement of the liver and spleen. Raised levels of lysine and arginine in urine are diagnostic of LPI as was seen in our patient. Another method of making a definitive diagnosis of LPI is confirming the presence of the mutated SLC7A7 gene by methods such as targeted mutation analysis and sequence analysis, which could not be done in our patient.  A suspicion of LPI was aroused when the child showed an inability to digest proteins, whereas clinical findings included a failure to thrive or grow, aversion to protein-rich foods, muscular hypotonia, early osteoporosis, pulmonary, and renal involvement. However, LPI may often be confused with other disorders such as hyperammonemia, lysosomal storage diseases, malabsorptive diseases, and autoimmune disorders, such as systemic lupus erythematosus,  which show similar clinical findings and so, a confirmed diagnosis of LPI requires the combination of the above-mentioned signs along with positive laboratory findings.
Treatment of LPI includes protein restriction; compensation for the loss of lysine and arginine involving carnitine supplementation, as it has been found to be effective by having a lysine-sparing effect. Citrulline has also been found effective as a treatment option in LPI as it is changed to arginine in our body. In case of an acute hyperammonemic crisis, pharmacologic treatment with arginine chloride, which blocks the production of ammonia and combination of nitrogen scavenger drugs sodium benzoate and sodium phenylacetate is suggested.  LPI is often associated with pulmonary and renal complications, and treatment of such complications with corticosteroids is found to be effective in some patients.  Therapy with bisphosphonates is currently under investigation as osteopenia leading to osteoporosis is a major feature. 
The prognosis of a child with LPI varies on the involvement of lung and the successful resolution of its complications, with pulmonary involvement representing an increased fatal outcome.  Being an autosomal recessive disorder, an antenatal diagnosis of LPI can be made by the DNA analysis of fetal cells extracted by amniocentesis usually performed at 15-18 weeks of gestation age.  In the scenario of this case, the patient was lost to follow-up and so his outcome could not be determined.
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