Journal Information
Vol. 94. Issue 3.
Pages 179-180 (1 March 2021)
Vol. 94. Issue 3.
Pages 179-180 (1 March 2021)
Scientific Letter
Open Access
Familial hypercholesterolaemia in twin brothers born using in-vitro fertilisation with donor semen and ovules
Hipercolesterolemia familiar en 2 hermanos mellizos nacidos por fecundación in vitro con semen yóvulos de donante
Pablo Alonso Rubioa,
Corresponding author

Corresponding author.
, Alba Megido Armadab, Eliecer Coto Garcíab, Isolina Riaño Galánb,c
a Hospital Carmen y Severo Ochoa, Cangas del Narcea, Asturias, Spain
b Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
c Comité de Bioética de la Asociación Española de Pediatría, Spain
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Assisted reproductive technology (ART) accounts for approximately 8% of births in Spain. The relative obscurity of these pregnancies and the anonymity of gamete donors, established by Spanish law on ART (in contrast with neighbouring countries), have given rise to new dilemmas in paediatric practice.1 The group of experts that reviewed the current situation of ART in Europe questioned the actual anonymity of gamete donors.2

We present 2 clinical cases that we consider of interest on account of the ethical aspects that it brought up following diagnosis of a genetic disorder in 2 siblings conceived through ART with donor sperm and eggs, and therefore with an unknown family history.

The patients were twins, one boy and one girl, referred to the paediatric endocrinology unit of tertiary care hospital after chance finding of high total cholesterol and low-density lipoprotein (LDL) levels. The relevant personal history included birth at 35 weeks with a weight adequate for gestational age following conception by in vitro fertilization (IVF) and a bichorial-diamniotic twin gestation. Neither patient had xanthomas. The girl was obese (body mass index z-score, +2.11). During the follow-up, the patient had sustained LDL levels of more than 190mg/dL despite implementation of dietary measures and daily physical activity. Suspicion of familial hypercholesterolaemia (FH) led to genetic testing with second-generation sequencing of LDL receptor, apolipoprotein B and proprotein convertase subtilisin/kexin type 9 genes. Testing detected a heterozygous pathogenic variant in exon 13 of the LDL receptor gene (p.Leu658Pro, c.1973T>C) in both patients, confirming the diagnosis of FH.

Familial hypercholesterolaemia is a genetic disorder that affects approximately 1 out of every 300 individuals in the general population. It is characterised by elevation of LDL levels from birth, the development of xanthomas and premature cardiovascular disease.3 It has an autosomal dominant pattern of inheritance, so that half of the offspring of an affected individual may develop the disorder. Most cases are caused by mutations in the LDL receptor gene, and de novo mutations in this gene are extremely rare.4 Since early diagnosis and treatment mitigate mitigating cardiovascular morbidity and mortality risk, diagnosis between ages 2 and 10 years is recommended.5 Despite the high risk of cardiovascular disease in these patients, most are undiagnosed and untreated.

Sperm and egg donors undergo a confidential evaluation that includes a physical examination and laboratory tests for detection of infectious and genetic diseases that could be transmitted to the offspring. Given the exponential growth in our knowledge of genetic changes, there is an ongoing debate as to the genetic screens that should be performed in gamete donors.2 Despite the high prevalence of FH and that it may be asymptomatic, current law does not mandate or contemplate genetic testing for this disease.

The diagnosis of FH in 2 siblings conceived through IVF from donor gametes posed a series of ethical dilemmas.

First, there is the harm caused to both patients through transmission of this disease, who will require lifelong treatment with dietary measures and lipid-lowering drugs.

Second, while the donation process is anonymous and confidential, Law 14/2006, of 26 May, on ART, establishes 2 situations in which the identity of the donor can be exceptionally revealed, with restrictions and without publicity: “certain danger to the life or the health of the child” and “as appropriate according to the law of criminal procedure”.6 Despite the risk of early cardiovascular disease of affected donors, the law does not contemplate disclosure of the identity of the donor on account of a health risk to the donor. We do not know whether the donor intentionally concealed the diagnosis of FH and chose not to provide truthful information about their health or was unaware of the condition. Either way, in this case, searching for the donors to inform them was not indicated.

On the other hand, there is the possibility that the gamete donor will transmit the disease to other offspring, although the law limits donation to a maximum of 6 offspring, including those conceived naturally or with ART.

In short, the situation presented here requires careful consideration of how we can prioritise the wellbeing of children conceived by ART.

S. Gallego Riestra, I. Riaño Galán.
¿Quién decide qué datos deben constar en la historia clínica en relación con el origen biológico?.
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Please cite this article as: Alonso Rubio P, Megido Armada A, Coto García E, Riaño Galán I. Hipercolesterolemia familiar en 2 hermanos mellizos nacidos por fecundación in vitro con semen yóvulos de donante. An Pediatr (Barc). 2021;94:179–180.

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