Jeff Bates MD, David Easley MD, & James Daniel MD

Case Report

Niemann-Pick disease (NPD) is a heterogeneous group of liposomal storage diseases caused by sphingomyelinase deficiency leading to deposits of sphingomyelin in the brain, liver, spleen, lungs, bone marrow and other visceral organs.  In the rarer Type Ib form of the disorder there is lack of the devastating nervous system involvement and the disease course is often less severe.  Although massive hepatosplenomegaly is often a presenting feature, significant compromise of liver function is uncommon.  We report here a patient with an unremarkable prenatal, birth, and family history with no known consanguinity who developed severe hepatic complications.

Initial presentation to clinic was with diarrhea and dehydration at 6 months of age.  Development of jaundice several days later led to further investigation.  Laboratory values revealed Aspartate aminotransferase (AST) 413 IU/L (normal values for our lab 10-42 IU/L), Alanine aminotransferase (ALT) 117 IU/L ( nl 10-60 IU/L), Alkaline Phosphatase 414IU/L (nl 42-360 IU/L), Total Bilirubin 10.5 mg/dL (nl 0.2-1.0 mg/dL), Direct Bilirubin 5.8 mg/dL (nl 0.0-0.2 mg/dL), Prothrombin time 16.8 sec (nl 10.0 - 12.1sec), and International Normalized Ratio 1.6 (nl 0.9 -1.1).  Referral was made to pediatric gastroenterology.  Hepatosplenomegaly was appreciated prompting further work up including percutaneous needle biopsy of the liver.

On light microscopy, multiple Kupffer cells were seen with increased vacuolation.  Vacuoles were negative for glycogen.  No obstructive changes were seen. Orcein, periodic acid-Schiff (PAS) and iron stains were unrevealing.  The biopsy also demonstrated early cirrhosis. Electron microscopy revealed normal glycogen and large droplet fatty changes.  Multiple dilated lysosomal cavities containing laminated myelin-like material were seen.  Finding were consistent with NPD.  Confirmatory assay using peripheral leukocyte sphingomyelinase activity was 0.07 micromoles/mg protein/hr (i.e. less than 10% of normal activity) compatible with the diagnosis of NPD type I.  On evaluation by pediatric neurology the patient had a normal neurological evaluation and no signs of developmental delay, consistent with a diagnosis of NPD type Ib.

Subsequent clinical course included moderate growth failure, mild developmental delay, multiple episodes of anemia requiring blood transfusions, and the development of portal hypertension as demonstrated on Doppler ultrasound.  With continued deterioration of hepatic function, the patient was evaluated for liver transplantation.  After initial evaluation, patient demonstrated progressive somnolence and irritability with hyperammonemia of 79 UMOL/L (nl 11-35 UMOL/L) consistent with hepatic encephalopathy.  Orthotopic liver transplant and splenectomy were performed at 2 years of age with subsequent marked clinical improvement.  She has had complete resolution of her growth failure and developmental delay.  There has been no recurrence of hepatic involvement or disease as evidenced by normal clinical exam, laboratory studies and multiple biopsies after transplantation.  She is now 2 years post transplant and doing well.

Editorial:

First, Niemann Pick disease is generally thought of as a pediatric zebra because the common Type A usually leads to death in the first few years of life.  However, Type B is less severe and numerous cases have been reported in the literature with no diagnosis made until adulthood, and is thus referred to as the Adult type by many.

Second, this particular case is of the common “adult type” but the patient presented in the first year of life.
 

Highlights of Previous Issues of The MedPeds Newsletter

Ambulatory training sites

These were followed in importance by Med/Peds faculty role models, a tertiary referral center, a combined Med/Peds clinic, the presence of a Children's Hospital, and community based ambulatory training sites.

The specific differences that stood out were that family practitioners felt significantly less comfortable than Med/Peds when it came to a "complex delivery room case". FP's were also less comfortable than med/peds with specific complex internal medicine problems. Med/Peds had higher confidence ratings in areas of complex cases of neonates and adults. Interestingly enough, there were no issues in which pediatricians felt more comfortable than Med/Peds. However, this was not true for internal medicine issues.

The flip side was as follows. FP's were more comfortable than Med/Peds with the routine care and psychosocial aspects of adolescent health care. There were also several issues in intensive care management of acute MI with which internal medicine physicians were more comfortable than Med/Peds.

While it is hard to draw conclusions from this study perhaps this can help us to guide our curriculum in these areas of less perceived confidence. While the guidelines already require a full month of adolescent care, the required ICU experiences are limited to 4 months in each field. These months should be maximized.

1. Schubiner H. Current positions of graduates of internal medicine-pediatrics training programs. Arch Pediatr Adolesc Med. 1997; 151:576-579.

2. Schubiner,H, Schuster, BL, Moncrease A, Mosca C. The perspectives of current trainees in combined internal medicine-pediatrics: results of a national survey. AJDC 1993;147:885-889.

3. Biro FM, Siegel DM, et al. A comparison of self-perceived clinical competencies in primary care residency graduates. Pediatric Research. 34(5):555-9, 1993 Nov.