The spectrum of free neuraminic acid storage disease in childhood: Clinical, morphological and biochemical observations in three non-Finnish patients

Abstract

N‐acetylneuraminic acid (sialic acid) storage disease is a rare autosomal recessive lysosomal disorder: Clinically two major forms exist, an infantile type with severe progression leading to early death, and a milder form (Salla disease) with a protracted course. Intermediate forms may also exist. Diagnosis rests on the determination of an excessive excretion of sialic acid in urine and concomitant storage in fibroblasts, the severe forms exhibiting the highest excretion and storage. We present clinical, morphological, and biochemical data on three non‐Finnish patients with sialic acid storage disease. Patient 1 was a preterm infant with neonatal ascites, coarse face, hepatosplenomegaly, pale skin, and wispy hair. vacuolated lymphocytes were abundant in a peripheral blood smear and he excreted large amounts of free sialic acid. High levels of free sialic acid were also found in cultured skin fibroblasts. He died at age 6 months from progressive respiratory insufficiency. Patient 2 was an 11‐month‐old Egyptian girl with coarse face, frequent upper respiratory tract infections, hepatosplenomegaly, and severe psychomotor retardation. Sialic acid excretion was elevated, likewise the storage in fibroblasts. histological investigations documented vacuolar storage in a skin biopsy and in iliac crest tissue. Patient 3 was a 16‐year‐old girl with slightly coarse face, severe generalized muscular hypotonia, ataxia, and kyphoscoliosis originally diagnosed as having post‐partum asphyxia. She suffered progressive motor function loss and had dysarthria. Urinary sialic acid was elevated and a skin biopsy demonstrated vacuolization. The clinical variability of sialic acid storage disease is exemplified by these three cases. Simple urinary screening for free sialic acid facilitates the diagnosis. The degree of urinary excretion may indeed correlate with clinical presentation and progression. © 1996 Wiley‐Liss, Inc.

Clinical, morphological, and molecular aspects of sialic acid storage disease manifesting in utero

“…6 Clinical data In contrast to our series (table 2), all the cases in the literature were diagnosed after birth, although the presence of antenatal signs was documented in 11 cases. [7][8][9][10][11][12][13][14][15][16] The earliest ultrasonographic sign was increased nuchal thickness at 10 GA preceding a more complete picture (case 11). The most prominent sign consisted of ascites discovered between 13 11 and 32 GA, 13 which could require repeated punctures in utero (our case 8 and case 2 of Lemyre et al 12 ) or at birth (case 4).…”

“…[7][8][9][10][11][12][13][14][15][16] The earliest ultrasonographic sign was increased nuchal thickness at 10 GA preceding a more complete picture (case 11). The most prominent sign consisted of ascites discovered between 13 11 and 32 GA, 13 which could require repeated punctures in utero (our case 8 and case 2 of Lemyre et al 12 ) or at birth (case 4). Antenatal ascites was absent in two of our four neonatal cases (although it was present at birth in case 2), in two further affected fetuses in families 2 and 7 at 12-13 GA, and in one case in the literature, 14 and was only transient in case 3 of Lemyre et al 12 In some cases, complete fetal hydrops was described, although it was never as severe as in our 21 cases of antenatal mucopolysaccharidosis VII (personal unpublished data) and never led to severe pulmonary hypoplasia.…”

Occurrence of sialic acids in healthy humans and different disorders

“…Salla's disease is a defective lysosomal membrane transport system for SA, in which the level of free SA in urine is about 5-to 10-fold compared with normal [42]. Sewell et al [43] have showed an increased urinary excretion of free SA and confirmed this in cultivated fibroblasts. In sialuria, a rare defect with excessive synthesis of SA, free ᮊ 1999 Blackwell Science Ltd, European Journal of Clinical Investigation, 29, 413-425 Table 2 Mean Ϯ SD, serum total SA (TSA), lipid-bound SA (LSA), TSA/total protein (TP) and protein-bound SA (PBSA) levels in healthy humans SA levels can be elevated 70-to 200-fold [44,45].…”

“…In these, SA accumulates in lysosomes, because of lysosome membrane not transporting SA. Although Salla's disease presents with neurological complications, but only slightly shortened lifespan, victims of infantile SA storage disorder possess a mean lifespan of 19 months, demonstrating a wide variety of symptoms [43,109]. In a rare condition of sialuria, excessive amounts of free SA is excreted in urine.…”

Serum and Saliva Levels of Sialic Acid Are Elevated in Alcoholics

“…On the other hand, measuring SA in urine is an established method for diagnosing inherited SA storage diseases such as Salla disease, sialuria, and sialidosis (Aula et al, 1979;Mancini et al, 1991;Krasnewich et al, 1993;Berra et al, 1995;Sewell et al, 1996). It is unclear why high alcohol consumption does not affect the urine levels of SA, whereas it affects the serum and saliva concentrations.…”