| Parameter . | Patient 1 . | Patient 2 . | Patient 3 . |
|---|---|---|---|
| Sex | Male | Male | Male |
| Current age | 17 yr | 21 yr | 10 mo |
| Consanguinity | None | None | None |
| Ethnicity | Caucasian | Caucasian | Caucasian |
| Mutation cDNA | c.293C>T | c.212G>A | c.212G>A |
| Mutation protein | p.Leu98Ser (L98S) | p. Arg71His (R71H) | p. Arg71His (R71H) |
| Glycosylation defect | IEF: tetrasialotransferrin: 34.2% (norm: 48.5–65.3%); trisialotransferrin: 28.9% (norm: 5.5–15.1%); disialotransferrin: 15% (norm: 2.0–6.1%); monosialotransferrin: 3.3% (norm: 0.0–3.7%); asialotransferrin: 1.5% (norm: 0%) | HPLC: tetrasialotransferrin 55.17% (norm: 85.7–94.0%); trisialotransferrin 33.11% (norm: 1.16–6.36%); disialotransferrin 8.92% (norm: 0.38–1.82%); monosialotransferrin 1.68% (norm: 0%) | HPLC: tetrasialotransferrin 35.7% (norm: 85.7–94.0%); trisialotransferrin 36.4% (norm: 1.16–6.36%); disialotransferrin 18.7% (norm: 0.38–1.82%); monosialotransferrin 9.0% (norm: 0%) |
| Onset of symptoms | 5 mo | Directly after birth | Directly after birth |
| Liver | Prolonged neonatal jaundice and persistent hepatosplenomegaly with recurrent episodes of hypoalbuminemia and ascites | No hepatomegaly in childhood, but liver parenchyma of an inhomogeneous, hyperechoic structure. | Prolonged neonatal jaundice and hepatosplenomegaly. Cholestasis. Irregular liver parenchyma with portosystemic shunts and ascites. Hypoalbuminemia, hyperammonemia. Coagulopathy. Listed for liver transplantation. |
| Today: hepatomegaly, mild elevation of liver enzymes | |||
| Liver biopsy | Micronodular hepatic cirrhosis with moderate macrovesicular steatosis (biopsy at 8 mo), elevated copper | Not available | Diffuse micronodular hepatic cirrhosis |
| Elevated copper | |||
| Neonatal icterus | + | - | + |
| Splenomegaly | + | + | + |
| Infections | Recurrent severe infections (e.g., sepsis, peritonitis) | Recurring pulmonary and upper respiratory tract infections throughout infancy and childhood | Recurring upper respiratory tract infections, positive blood cultures with pneumococcus at one occasion |
| Neurological symptoms | Mild cognitive impairment | Ataxic gait, mild cognitive impairment | Normal |
| Cutis laxa | Mild to moderate | Pronounced, improvement over time | Pronounced |
| Hypogammaglo-bulinemia | + | + | - |
| IgG | 2.31 g/L (reference: 5.6–13.8 g/L) | Reduced IgG1 and IgG3 | - |
| IgM | <0.17 g/L | 18 mg/dl (reference: 40–230 mg/dl) | - |
| IgA | <0.08 g/L | <15 mg/dl (reference: 70–400 mg/dl) | - |
| Increased transaminases | At 17 yr, mild elevation of transaminases (AST 61 U/l [reference: 15–46 UI/l], ALT 51 U/l [reference: 10–40 U/l]) | Ranging from mild elevation at age 9 yr: AST 92 U/l (reference: 8–60 U/l), ALT 59 U/l (reference: <44 U/l) to pronounced hepatic affection (AST 135 U/l) | Within the first year: AST 100–160 U/l, (reference: <71 U/l) |
| Serum copper | Not available | At 1 yr: 1.5 µmol/l (reference: 10–30 µmol/l) | Normal serum copper at the age of 4 mo: 89 µg/dl (reference: 65–165 µg/dl) |
| Normalized over the following months | |||
| Serum lipids | At age 17 yr (liver normal): | At age 20 yr: | At age 5 mo: |
| Cholesterol: 172 (reference: 200 mg/dl) | Cholesterol: 199 (reference: 200 mg/dl) | Cholesterol: 254 (reference: 81–147 mg/dl) | |
| LDL-cholesterol: 90 (reference: 50–130 md/dl) | LDL-cholesterol: 149 (reference: 50–130 md/dl) | ||
| Other laboratory findings | Low factor V and VI | Low factor XI (58% [reference: >70%]) and free protein S (57.5% [reference: 60–140%]) | Low factors II (27.7% [reference: 60–120%]), V (35.9% [reference: 55–130%]), VII (21.9% [reference: 47–130%]), IX (17.27% [reference: 36–136%]), and XI (23.9% [reference: 49–134%]) |
| Factor V: 30% (reference: 65–148%), factor VII: 24% (reference: 58–115%) | |||
| Other clinical findings | Mild dysmorphic features | Low-set ears, micrognathia, a flat and wide-set chest, laterally facing nipples, and hypospadia |
| Parameter . | Patient 1 . | Patient 2 . | Patient 3 . |
|---|---|---|---|
| Sex | Male | Male | Male |
| Current age | 17 yr | 21 yr | 10 mo |
| Consanguinity | None | None | None |
| Ethnicity | Caucasian | Caucasian | Caucasian |
| Mutation cDNA | c.293C>T | c.212G>A | c.212G>A |
| Mutation protein | p.Leu98Ser (L98S) | p. Arg71His (R71H) | p. Arg71His (R71H) |
| Glycosylation defect | IEF: tetrasialotransferrin: 34.2% (norm: 48.5–65.3%); trisialotransferrin: 28.9% (norm: 5.5–15.1%); disialotransferrin: 15% (norm: 2.0–6.1%); monosialotransferrin: 3.3% (norm: 0.0–3.7%); asialotransferrin: 1.5% (norm: 0%) | HPLC: tetrasialotransferrin 55.17% (norm: 85.7–94.0%); trisialotransferrin 33.11% (norm: 1.16–6.36%); disialotransferrin 8.92% (norm: 0.38–1.82%); monosialotransferrin 1.68% (norm: 0%) | HPLC: tetrasialotransferrin 35.7% (norm: 85.7–94.0%); trisialotransferrin 36.4% (norm: 1.16–6.36%); disialotransferrin 18.7% (norm: 0.38–1.82%); monosialotransferrin 9.0% (norm: 0%) |
| Onset of symptoms | 5 mo | Directly after birth | Directly after birth |
| Liver | Prolonged neonatal jaundice and persistent hepatosplenomegaly with recurrent episodes of hypoalbuminemia and ascites | No hepatomegaly in childhood, but liver parenchyma of an inhomogeneous, hyperechoic structure. | Prolonged neonatal jaundice and hepatosplenomegaly. Cholestasis. Irregular liver parenchyma with portosystemic shunts and ascites. Hypoalbuminemia, hyperammonemia. Coagulopathy. Listed for liver transplantation. |
| Today: hepatomegaly, mild elevation of liver enzymes | |||
| Liver biopsy | Micronodular hepatic cirrhosis with moderate macrovesicular steatosis (biopsy at 8 mo), elevated copper | Not available | Diffuse micronodular hepatic cirrhosis |
| Elevated copper | |||
| Neonatal icterus | + | - | + |
| Splenomegaly | + | + | + |
| Infections | Recurrent severe infections (e.g., sepsis, peritonitis) | Recurring pulmonary and upper respiratory tract infections throughout infancy and childhood | Recurring upper respiratory tract infections, positive blood cultures with pneumococcus at one occasion |
| Neurological symptoms | Mild cognitive impairment | Ataxic gait, mild cognitive impairment | Normal |
| Cutis laxa | Mild to moderate | Pronounced, improvement over time | Pronounced |
| Hypogammaglo-bulinemia | + | + | - |
| IgG | 2.31 g/L (reference: 5.6–13.8 g/L) | Reduced IgG1 and IgG3 | - |
| IgM | <0.17 g/L | 18 mg/dl (reference: 40–230 mg/dl) | - |
| IgA | <0.08 g/L | <15 mg/dl (reference: 70–400 mg/dl) | - |
| Increased transaminases | At 17 yr, mild elevation of transaminases (AST 61 U/l [reference: 15–46 UI/l], ALT 51 U/l [reference: 10–40 U/l]) | Ranging from mild elevation at age 9 yr: AST 92 U/l (reference: 8–60 U/l), ALT 59 U/l (reference: <44 U/l) to pronounced hepatic affection (AST 135 U/l) | Within the first year: AST 100–160 U/l, (reference: <71 U/l) |
| Serum copper | Not available | At 1 yr: 1.5 µmol/l (reference: 10–30 µmol/l) | Normal serum copper at the age of 4 mo: 89 µg/dl (reference: 65–165 µg/dl) |
| Normalized over the following months | |||
| Serum lipids | At age 17 yr (liver normal): | At age 20 yr: | At age 5 mo: |
| Cholesterol: 172 (reference: 200 mg/dl) | Cholesterol: 199 (reference: 200 mg/dl) | Cholesterol: 254 (reference: 81–147 mg/dl) | |
| LDL-cholesterol: 90 (reference: 50–130 md/dl) | LDL-cholesterol: 149 (reference: 50–130 md/dl) | ||
| Other laboratory findings | Low factor V and VI | Low factor XI (58% [reference: >70%]) and free protein S (57.5% [reference: 60–140%]) | Low factors II (27.7% [reference: 60–120%]), V (35.9% [reference: 55–130%]), VII (21.9% [reference: 47–130%]), IX (17.27% [reference: 36–136%]), and XI (23.9% [reference: 49–134%]) |
| Factor V: 30% (reference: 65–148%), factor VII: 24% (reference: 58–115%) | |||
| Other clinical findings | Mild dysmorphic features | Low-set ears, micrognathia, a flat and wide-set chest, laterally facing nipples, and hypospadia |
IEF, isoelectric focusing.